Objectives: 1). Chemically modify Acinetobacter glutaminase- asparaginase and E. coli asparaginase. Develop efficient methods for coupling the enzymes to soluble polymers and insoluble hydrogel matrices with biologically stable bonding and retention of high enzymatic activity. Also chemically modify specific groups on the enzymes. 2). Systematically study the amount of enzyme per unit area, the composition of the hydrogel and the length of an intermediate arm between the enzyme and the hydrogel on the antitumor activity and biocompatibility of the shunt. 3). Characterize the kinetic and physical properties of the modified enzymes. 4). Determine the immune response of animals to the variously modified enzymes. Assess the levels of circulating anti- enzyme antibodies, the levels of mast cell sensitizing antibodies and the extent of the cellular immune response. Determine the role of the immune response in limiting the efficacy of modified antitumor enzymes on repeated exposure of experimental animals. 5). Evaluate the influence of the soluble modifications of the enzymes on clearance from the circulation and distribution in tissues. 6). Compare the toxic effects of modified and native enzymes. 7). Compare the antitumor effects and amino acid depletion of modified and native enzymes.